John P. Kress, M.D., Instructor of Medicine in the Section of Pulmonary and Critical Care Medicine of the University of Chicago, seeks support for research training in order to establish a career as a clinical investigator examining issues related to the care of critically ill patients. In order to enhance his research skills, Dr. Kress will meet regularly with his mentor, Dr. Jesse Hall, a nationally regarded critical care clinical investigator and Chief of the Section of Pulmonary and Critical Care Medicine. He will also enroll in the certificate program sponsored by the University's NIH-funded Clinical Research Training Program. Dr. Kress's research proposal describes several studies assessing practical strategies for sedation of critically ill patients that optimize efficacy and minimize complications. The specific aims of this proposal include a further evaluation of the strategy of daily sedative interruption recently described by Dr. Kress and colleagues, which was found to significantly reduce duration of mechanical ventilation and intensive care unit length of stay. Dr. Kress will attempt to uncover problems with the strategy of daily sedative interruption, with a focus on long term psychological maladjustments in patients exposed to daily interruption of sedative infusions and acute myocardial ischemia during the time of daily sedative interruption. He will also study outcomes of critically ill patients sedated by a strategy of intermittent bolus administration of sedatives versus a strategy of continuous infusion of sedatives with a daily scheduled interruption. These studies focus on practical bedside strategies that can be undertaken in a wide variety of settings. The goal of this project will be to develop and test strategies that attempt to assure optimal patient comfort while reducing complications of sedative drug administration in critically ill patients who frequently manifest altered, unpredictable pharmacokinetics and pharmacodynamics.